Surgery Combined With Maintenance Targeted Therapy in the Treatment of Advanced Ovarian Cancer

Official title

A Prospective, Multicenter, Randomized Phase II Trial on Optimal Timing of Surgery Combined With Maintenance Targeted Therapy in the Treatment of Advanced Ovarian Cancer

Overview

Optimal Timing of Surgery combined with Maintenance Therapy in the Front-line Treatment of Advanced Ovarian Cancer

Detailed description

The purpose of this trial is to answer the fundamental question 'The Optimal Timing of Surgery' combined with Bevacizumab or Poly-adenosine Ribose Phosphate Inhbitors (PARPi), in the circumstance of primarily diagnosed advanced epithelial ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma.

Interventions

• Procedure Primary debulking surgery
  Primary debulking surgery with a maximum cytoreduction, then followed by 6 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5.
• Procedure Neoadjuvant chemotherapy
  3 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5, Interval debulking surgery with a maximal cytoreduction of complete gross resection, then followed by another 3 cycles of chemotherapy.
• Drug PARP inhibitor
  For patients with BRCA mutated, maintenance therapy of PARP inhibitors following CR/PR after first-line chemotherapy. In this trial, Olaparib 300mg p.o. twice daily is suggested after the front-line therapy.
• Drug Bevacizumab
  For patients without BRCA mutated, maintenance therapy of Bevacizumab following CR/PR after first-line chemotherapy. In this trial, Bevacizumab 7.5mg per kilogram intravenous once every 3 weeks is suggested after the front-line therapy.

Primary outcome measures

• 3-year overall survival [Time frame: Participants will be followed for at least 3 years after randomization]

Secondary outcome measures (8)

• Overall survival [Time frame: Participants will be followed for at least 3 years after randomization]
• Progression-free survival [Time frame: Participants will be followed for at least 3 years after randomization]
• Post-operative complications [Time frame: Participants will be followed up to 3 months after randomization]
• Quality of life assessments [Time frame: Participants will be followed for at least 3 years after randomization]
• Accumulated treatment-free survival [Time frame: Participants will be followed for at least 3 years or death after randomization]
• TFST [Time frame: Participants will be followed for at least 3 years or death after randomization]
• TSST [Time frame: Participants will be followed for at least 3 years or death after randomization]
• The pattern of the first relapse [Time frame: Participants will be followed for at least 3 years or death after randomization]

Eligibility criteria

Inclusion criteria

• Females aged ≥ 18 years.
• Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma
• Low, Middle tumor burden and high tumor burden with cPCI score ≤ 12 based on pre-operative CT or PET/CT examination
• Complete cytoreduction can be achieved based on CT or PET/CT examination
• Patients must agree to undergo BRCA (breast cancer gene) and HRD (homologous recombination deficiency) testing
• Performance status (ECOG 0-2)
• Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery:

• white blood cells >3,000/µL, absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL, hemoglobin ≥9 g/dL,
• serum creatinine <1.25 x upper normal limit (UNL) or creatinine clearance ≥60 mL/min according to Cockroft-Gault formula or to local lab measurement,
• serum bilirubin <1.25 x UNL, AST(SGOT) and ALT(SGPT) <2.5 x UNL.
• Comply with the study protocol and follow-up.
• Patients who have given their written informed consent.

Exclusion criteria

• Non-epithelial ovarian malignancies and borderline tumors
• Low grade ovarian cancer
• Mucinous ovarian cancer
• Complete cytoreduction cannot be achieved according to preoperative evaluation, including pulmonary and hepatic parenchymal metastases, unresectable extensive pleural metastases, multiple thoracic lymph nodes metastases, brain or bone metastases
• Patient has a known hypersensitivity to the components of olaparib/bevacizumab or its excipients
• Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ, thyroid carcinoma, or breast carcinoma (without any signs of relapse or activity, early-stage).
• Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise adherence to the protocol.
• Other conditions, such as religious, psychological, and other factors, that could interfere with the provision of informed consent, compliance to study procedures, or follow-up.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 9 centers

• The First People's Hospital of Foshan — Foshan
• Sun Yet-Sen University Cancer Center — Guangzhou
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou
• Zhejiang Cancer Hospital — Hangzhou
• The First Affiliated Hospital of University of Science and Technology of China — Hefei
• Fudan University Cancer Hospital — Shanghai
• Obstetrics and Gynecology Hospital of Fundan University — Shanghai
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai
• … and 1 more center

Identifiers

NCT: NCT05200260 · SAT-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗